System and method for timing synchronized pacing

ABSTRACT

A device and method for cardiac rhythm management in which a heart chamber is paced in accordance with sense signals from the opposite chamber or other distant cardiac site. The method is particularly useful in delivering cardiac resynchronization therapy.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application is a divisional of U.S. patent application Ser. No.10/864,849, filed on Jun. 9, 2004, now issued as U.S. Pat. No.7,392,083, which is a continuation of U.S. patent application Ser. No.10/454,014, filed on Jun. 3, 2003, now issued as U.S. Pat. No.7,158,828, which is a continuation of U.S. patent application Ser. No.09/748,736, filed on Dec. 26, 2000, now issued as U.S. Pat. No.6,574,506, the specifications of which are incorporated herein byreference.

FIELD OF THE INVENTION

This invention pertains to methods and apparatus for cardiac rhythmmanagement. In particular, the invention relates to methods andapparatus for providing cardiac resynchronization therapy.

BACKGROUND

Cardiac rhythm management devices are implantable devices that provideelectrical stimulation to selected chambers of the heart in order totreat disorders of cardiac rhythm and include pacemakers and implantablecardioverter/defibrillators. A pacemaker is a cardiac rhythm managementdevice that paces the heart with timed pacing pulses. The most commoncondition for which pacemakers are used is in the treatment ofbradycardia, where the ventricular rate is too slow. Atrio-ventricularconduction defects (i.e., AV block) that are permanent or intermittentand sick sinus syndrome represent the most common causes of bradycardiafor which permanent pacing may be indicated. If functioning properly,the pacemaker makes up for the heart's inability to pace itself at anappropriate rhythm in order to meet metabolic demand by enforcing aminimum heart rate. Pacing therapy may also be applied in order to treatcardiac rhythms that are too fast, termed anti-tachycardia pacing. (Asthe term is used herein, a pacemaker is any cardiac rhythm managementdevice with a pacing functionality, regardless of any other functions itmay perform such as the delivery cardioversion or defibrillation shocksto terminate atrial or ventricular fibrillation.)

Also included within the concept of cardiac rhythm is the manner anddegree to which the heart chambers contract during a cardiac cycle toresult in the efficient pumping of blood. For example, the heart pumpsmore effectively when the chambers contract in a coordinated manner. Theheart has specialized conduction pathways in both the atria and theventricles that enable the rapid conduction of excitation (i.e.,depolarization) throughout the myocardium. These pathways conductexcitatory impulses from the sino-atrial node to the atrial myocardium,to the atrio-ventricular node, and thence to the ventricular myocardiumto result in a coordinated contraction of both atria and bothventricles. This both synchronizes the contractions of the muscle fibersof each chamber and synchronizes the contraction of each atrium orventricle with the contralateral atrium or ventricle. Without thesynchronization afforded by the normally functioning specializedconduction pathways, the heart's pumping efficiency is greatlydiminished. Patients who exhibit pathology of these conduction pathways,such as bundle branch blocks, can thus suffer compromised cardiacoutput.

Patients with conventional pacemakers can also have compromised cardiacoutput because artificial pacing with an electrode fixed into an area ofthe myocardium does not take advantage of the above-describedspecialized conduction system. The spread of excitation from a singlepacing site must proceed only via the much slower conducting musclefibers of either the atria or the ventricles, resulting in the part ofthe myocardium stimulated by the pacing electrode contracting wellbefore parts of the chamber located more distally to the electrode,including the myocardium of the chamber contralateral to the pacingsite. Although the pumping efficiency of the heart is somewhat reducedfrom the optimum, most patients can still maintain more than adequatecardiac output with artificial pacing.

Heart failure is a clinical syndrome in which an abnormality of cardiacfunction causes cardiac output to fall below a level adequate to meetthe metabolic demand of peripheral tissues and is usually referred to ascongestive heart failure (CHF) due to the accompanying venous andpulmonary congestion. CHF can be due to a variety of etiologies withischemic heart disease being the most common. Some CHF patients sufferfrom some degree of AV block or are chronotropically deficient such thattheir cardiac output can be improved with conventional bradycardiapacing. Such pacing, however, may result in some degree ofuncoordination in atrial and/or ventricular contractions due to the wayin which pacing excitation is spread throughout the myocardium asdescribed above. The resulting diminishment in cardiac output may besignificant in a CHF patient whose cardiac output is alreadycompromised. Intraventricular and/or interventricular conduction defectsare also commonly found in CHF patients. In order to treat theseproblems, cardiac rhythm management devices have been developed whichprovide electrical pacing stimulation to one or more heart chambers inan attempt to improve the coordination of atrial and/or ventricularcontractions, termed cardiac resynchronization therapy.

SUMMARY OF THE INVENTION

Cardiac resynchronization therapy can most conveniently be delivered bya cardiac rhythm management device in accordance with a bradycardiapacing mode so that the activation patterns between and within selectedheart chambers are both resynchronized and paced concurrently. Inaccordance with the invention, one heart chamber, designated as the ratechamber, is paced with a bradycardia mode while the contralateralchamber or other pacing site, designated as the synchronized chamber orsynchronized site, is paced with a synchronized pacing mode such that apace is delivered at a specified pacing instant defined with respect toexpiration of a rate chamber escape interval based upon rate chamberevents. The rate chamber escape interval may be reset by a rate chambersense or a pace to either chamber. This allows the rate at which thesynchronized chamber is paced to be controlled only by intrinsicactivity in the rate chamber. Because the synchronized chamber pace isnot triggered by a rate chamber sense signal in this mode, the pacinginstant for the synchronized chamber pace can be defined variably withrespect to an accompanying rate chamber pace by a synchronized chamberoffset interval. The synchronized chamber offset interval may be zero,positive, or negative so that the synchronized chamber is pacedsimultaneous with, after, or before the rate chamber is paced. The ratechamber may also be pseudo-paced such that the same timing is effectedas with offset pacing, but only the synchronized chamber is paced. Theuse of a singe rate chamber for timing purposes not only facilitates thedesired resynchronization of the synchronized chamber, but also allowsthe use of common timing and timing markers across multiple cardiacrhythm management therapies, such as tachycardia and bradycardia pacing.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a system diagram of a pacemaker configured for biventricularpacing and sensing.

FIGS. 2, 3, 4, 5A, 5B, 6, 7, 8A, 8B and 8C illustrate timing diagrams ofdifferent synchronized pacing modes.

DESCRIPTION OF THE INVENTION

When one heart chamber is paced and the contralateral chamber is notpaced, the paced chamber contracts earlier than the opposite chamber,which creates an uncoordinated bilateral contraction sequence thatdeteriorates heart pumping function. To help prevent this deterioration,devices have been made to pace both right and left chamberssimultaneously. Such devices employ the normal pacemaker bradycardiapacing modes to set the rate of simultaneous right and left ventricularpaced pulses. One such mode is a synchronous pacing mode, which inhibitsand reschedules pacing when an intrinsic depolarization is sensed at thepacing site prior to pacing that site.

For some applications, including resynchronization of bilateralcontraction sequence, it may be advantageous to pace with short delaysbetween right and left pacing pulses, with either the right or leftchamber being paced first. Problems arise when the right and leftchambers are to be paced non-simultaneously with a synchronousbradycardia mode, because intrinsic depolarizations sensed in eitherchamber will inhibit and reset pacing in both chambers. For example, thepacing rate will vary depending on whether a sense occurred first in theright chamber or the left chamber. Also it may be important to deliver apace to one chamber even though a sense occurred in the oppositechamber. In accordance with the present invention, right and leftchambers are paced non-simultaneously with pacing rate based on sensingfrom only one of the bilateral chambers, designated the rate chamber,and pacing of the opposite chamber, designated the synchronized chamber,is synchronized by an offset interval to the rate chamber pacing. Forexample, a synchronous mode pacing rate will be determined only by therate chamber sensing, and pacing can occur in the rate chamber even whenan intrinsic depolarization is sensed first in the opposite chamber.Also in accordance with the present invention, while basing the pacingrate on sensing from only one of the bilateral chambers, it is possiblealso to pace either chamber after a short delay following sensing of anintrinsic depolarization in the contralateral chamber. This provisionextends the flexibility to pace one chamber even after a sense in theopposite chamber. All these provisions pertain more generally to amultisite pacing device that provides for multiple pacing sites withinone or more paired heart chambers wherein intrinsic depolarizationssensed from only one site is used to set the pacing rate. All otherpacing sites are paced synchronized by offset intervals to the pacing atthe site having rate sensing.

A problem that arises when a pacing instant for a synchronized heartchamber or other synchronized site is based upon whether or not a sensesignal is received only from the contralateral rate chamber (or distantrate site within the same chamber as the synchronized site) is that therisk of a pace being delivered near the time of a prior contraction andduring a vulnerable period is increased. This is because the pacing of asynchronized site is then neither inhibited nor triggered by intrinsicactivity at that site, which activity may occur sooner or later thanthat of the rate site during a particular cardiac cycle. In accordancewith the present invention, a protection period begins after the sensingof intrinsic activity at the synchronized site to be paced. Theprotection period then prevents any pacing from being delivered to thesynchronized site for the duration of the period. Pacing of thesynchronized site is then inhibited in a manner that does not otherwisedisturb the pacing algorithm.

1. Hardware Platform

Pacemakers are typically implanted subcutaneously on a patient's chestand have leads threaded intravenously into the heart to connect thedevice to electrodes used for sensing and pacing. A programmableelectronic controller causes the pacing pulses to be output in responseto lapsed time intervals and sensed electrical activity (i.e., intrinsicheart beats not as a result of a pacing pulse). Pacemakers senseintrinsic cardiac electrical activity by means of internal electrodesdisposed near the chamber to be sensed. A depolarization wave associatedwith an intrinsic contraction of the atria or ventricles that isdetected by the pacemaker is referred to as an atrial sense orventricular sense, respectively. In order to cause such a contraction inthe absence of an intrinsic beat, a pacing pulse (either an atrial paceor a ventricular pace) with energy above a certain pacing threshold isdelivered to the chamber.

FIG. 1 shows a system diagram of a microprocessor-based pacemakerphysically configured with sensing and pacing channels for both atriaand both ventricles. The controller 10 of the pacemaker is amicroprocessor which communicates with a memory 12 via a bidirectionaldata bus. The memory 12 typically comprises a ROM (read-only memory) forprogram storage and a RAM (random-access memory) for data storage. Thepacemaker has atrial sensing and pacing channels comprising electrode 34a-b, leads 33 a-b, sensing amplifiers 31 a-b, pulse generators 32 a-b,and atrial channel interfaces 30 a-b which communicate bidirectionallywith microprocessor 10. The device also has ventricular sensing andpacing channels for both ventricles comprising electrodes 24 a-b, leads23 a-b, sensing amplifiers 21 a-b, pulse generators 22 a-b, andventricular channel interfaces 20 a-b. In the figure, “a” designates oneventricular or atrial channel and “b” designates the channel for thecontralateral chamber. In this embodiment, a single electrode is usedfor sensing and pacing in each channel, known as a unipolar lead. Otherembodiments may employ bipolar leads which include two electrodes foroutputting a pacing pulse and/or sensing intrinsic activity. The channelinterfaces 20 a-b and 30 a-b include analog-to-digital converters fordigitizing sensing signal inputs from the sensing amplifiers andregisters that can be written to by the microprocessor in order tooutput pacing pulses, change the pacing pulse amplitude, and adjust thegain and threshold values for the sensing amplifiers. An exertion levelsensor 330 (e.g., an accelerometer, a minute ventilation sensor, orother sensor that measures a parameter related to metabolic demand)enables the controller to adapt the pacing rate in accordance withchanges in the patient's physical activity. A telemetry interface 40 isalso provided for communicating with an external programmer 500 whichhas an associated display 510. A pacemaker incorporating the presentinvention may possess all of the components in FIG. 1 and beprogrammable so as to operate in a number of different modes, or it mayhave only those components necessary to operate in a particular mode.

The controller 10 controls the overall operation of the device inaccordance with programmed instructions stored in memory. The controller10 controls the delivery of paces via the pacing channels, interpretssense signals from the sensing channels, implements timers for definingescape intervals and sensory refractory periods, and performs the pacecounting functions as described below. It should be appreciated,however, that these functions could also be performed by custom logiccircuitry either in addition to or instead of a programmedmicroprocessor.

2. Bradycardia Pacing Modes

Bradycardia pacing modes refer to pacing algorithms used to pace theatria and/or ventricles when the intrinsic atrial and/or ventricularrate is inadequate due to, for example, sinus node dysfunction or AVconduction blocks. Such modes may either be single-chamber pacing, whereeither an atrium or a ventricle is paced, or dual-chamber pacing inwhich both an atrium and a ventricle are paced. The modes are generallydesignated by a letter code of three positions where each letter in thecode refers to a specific function of the pacemaker. The first letterrefers to which heart chambers are paced and which may be an A (foratrium), a V (for ventricle), D (for both chambers), or (for none). Thesecond letter refers to which chambers are sensed by the pacemaker'ssensing channels and uses the same letter designations as used forpacing. The third letter refers to the pacemaker's response to a sensedP wave from the atrium or an R wave from the ventricle and may be an I(for inhibited), T (for triggered), D (for dual in which both triggeringand inhibition are used), and O (for no response). Modern pacemakers aretypically programmable so that they can operate in any mode which thephysical configuration of the device will allow. Additional sensing ofphysiological data allows some pacemakers to change the rate at whichthey pace the heart in accordance with some parameter correlated tometabolic demand. Such pacemakers are called rate-adaptive pacemakersand are designated by a fourth letter added to the three-letter code, R.

Pacemakers can enforce a minimum heart rate either asynchronously orsynchronously. In asynchronous pacing, the heart is paced at a fixedrate irrespective of intrinsic cardiac activity. There is thus a riskwith asynchronous pacing that a pacing pulse will be deliveredcoincident with an intrinsic beat and during the heart's vulnerableperiod which may cause fibrillation. Most pacemakers for treatingbradycardia today are therefore programmed to operate synchronously in aso-called demand mode where sensed cardiac events occurring within adefined interval either trigger or inhibit a pacing pulse. Inhibiteddemand pacing modes utilize escape intervals to control pacing inaccordance with sensed intrinsic activity. In an inhibited demand mode,a pacing pulse is delivered to a heart chamber during a cardiac cycleonly after expiration of a defined escape interval during which nointrinsic beat by the chamber is detected. If an intrinsic beat occursduring this interval, the heart is thus allowed to “escape” from pacingby the pacemaker. Such an escape interval can be defined for each pacedchamber. For example, a ventricular escape interval can be definedbetween ventricular events so as to be restarted with each ventricularsense or pace. The inverse of this escape interval is the minimum rateat which the pacemaker will allow the ventricles to beat, sometimesreferred to as the lower rate limit (LRL).

In atrial tracking pacemakers (i.e., VDD or DDD mode), anotherventricular escape interval is defined between atrial and ventricularevents, referred to as the atrio-ventricular interval (AVI). Theatrio-ventricular interval is triggered by an atrial sense or pace andstopped by a ventricular sense or pace. A ventricular pace is deliveredupon expiration of the atrio-ventricular interval if no ventricularsense occurs before. Atrial-tracking ventricular pacing attempts tomaintain the atrio-ventricular synchrony occurring with physiologicalbeats whereby atrial contractions augment diastolic filling of theventricles. If a patient has a physiologically normal atrial rhythm,atrial-tracking pacing also allows the ventricular pacing rate to beresponsive to the metabolic needs of the body.

A pacemaker can also be configured to pace the atria on an inhibiteddemand basis. An atrial escape interval is then defined as the maximumtime interval in which an atrial sense must be detected after aventricular sense or pace before an atrial pace will be delivered. Whenatrial inhibited demand pacing is combined with atrial-triggeredventricular demand pacing (i.e., DDD mode), the lower rate limitinterval is then the sum of the atrial escape interval and theatrio-ventricular interval.

Another type of synchronous pacing is atrial-triggered orventricular-triggered pacing. In this mode, an atrium or ventricle ispaced immediately after an intrinsic beat is detected in the respectivechamber. Triggered pacing of a heart chamber is normally combined withinhibited demand pacing so that a pace is also delivered upon expirationof an escape interval in which no intrinsic beat occurs. Such triggeredpacing may be employed as a safer alternative to asynchronous pacingwhen, due to far-field sensing of electromagnetic interference fromexternal sources or skeletal muscle, false inhibition of pacing pulsesis a problem. If a sense in the chamber's sensing channel is an actualdepolarization and not a far-field sense, the triggered pace isdelivered during the chamber's physiological refractory period and is ofno consequence.

Finally, rate-adaptive algorithms may be used in conjunction withbradycardia pacing modes. Rate-adaptive pacemakers modulate theventricular and/or atrial escape intervals based upon measurementscorresponding to physical activity. Such pacemakers are applicable tosituations in which intrinsic atrial rates are unreliable orpathological. In a rate-adaptive pacemaker, for example, the LRL isadjusted in accordance with exertion level measurements such as from anaccelerometer or minute ventilation sensor in order for the heart rateto more nearly match metabolic demand. The adjusted LRL is then termedthe sensor-indicated rate.

3. Cardiac Resynchronization Therapy

Cardiac resynchronization therapy is pacing stimulation applied to oneor more heart chambers in a manner that restores or maintainssynchronized bilateral contractions of the atria and/or ventricles andthereby improves pumping efficiency. Certain patients with conductionabnormalities may experience improved cardiac synchronization withconventional single-chamber or dual-chamber pacing as described above.For example, a patient with left bundle branch block may have a morecoordinated contraction of the ventricles with a pace than as a resultof an intrinsic contraction. In that sense, conventional bradycardiapacing of an atrium and/or a ventricle may be considered asresynchronization therapy. Resynchronization pacing, however, may alsoinvolve pacing both ventricles and/or both atria in accordance with asynchronized pacing mode as described below. A single chamber may alsobe resynchronized to compensate for intra-atrial or intra-ventricularconduction delays by delivering paces to multiple sites of the chamber.

Other therapeutic alterations of cardiac function through multisitepacing changes in activation and contraction sequences are included inthe meaning of cardiac resynchronization therapy. For instance, pacingat more than one site within a heart chamber to desynchronize thecontraction sequence of that chamber may be therapeutic in patients withhypertrophic obstructive cardiomyopathy, where creating asynchronouscontractions with multi-site pacing reduces the abnormalhyper-contractile function of the chamber. Similarly altering bilateralcontraction sequences or intrachamber contraction sequences bypre-exciting one site relative to another site may be used to alter theregional workload and metabolic energy demand of the pre-excited regionin order to allow regions of damaged heart tissue to recover from injuryor disease.

It is advantageous to deliver resynchronization therapy in conjunctionwith one or more synchronous bradycardia pacing modes, such as aredescribed above. One atrial and/or one ventricular sites are designatedas rate sites, and paces are delivered to the rate sites based uponpacing and sensed intrinsic activity at the site in accordance with thebradycardia pacing mode. In a single-chamber bradycardia pacing mode,for example, one of the paired atria or one of the ventricles isdesignated as the rate chamber. In a dual-chamber bradycardia pacingmode, either the right or left atrium is selected as the atrial ratechamber and either the right or left ventricle is selected as theventricular rate chamber. The heart rate and the escape intervals forthe pacing mode are defined by intervals between sensed and paced eventsin the rate chambers only. Resynchronization therapy may then beimplemented by adding synchronized pacing to the bradycardia pacing modewhere paces are delivered to one or more synchronized pacing sites in adefined time relation to one or more selected sensing and pacing eventsthat either reset escape intervals or trigger paces in the bradycardiapacing mode. Multiple synchronized sites may be paced through multiplesynchronized sensing/pacing channels, and the multiple synchronizedsites may be in the same or different chambers as the rate site.

In bilateral synchronized pacing, which may be either biatrial orbiventricular synchronized pacing, the heart chamber contralateral tothe rate chamber is designated as a synchronized chamber. For example,the right ventricle may be designated as the rate ventricle and the leftventricle designated as the synchronized ventricle, and the paired atriamay be similarly designated. Each synchronized chamber is then paced ina timed relation to a pace or sense occurring in the contralateral ratechamber in accordance with a synchronized pacing mode as describedbelow.

One synchronized pacing mode may be termed offset synchronized pacing.In this mode, the synchronized chamber is paced with a positive,negative, or zero timing offset as measured from a pace delivered to itspaired rate chamber, referred to as the synchronized chamber offsetinterval. The offset interval may be zero in order to pace both chamberssimultaneously, positive in order to pace the synchronized chamber afterthe rate chamber, or negative to pace the synchronized chamber beforethe rate chamber. One example of such pacing is biventricular offsetsynchronized pacing where both ventricles are paced with a specifiedoffset interval. The rate ventricle is paced in accordance with asynchronous bradycardia mode which may include atrial tracking, and theventricular escape interval is reset with either a pace or a sense inthe rate ventricle. (Resetting in this context refers to restarting theinterval in the case of an LRL ventricular escape interval and tostopping the interval in the case of an AVI.) Thus, a pair ofventricular paces are delivered after expiration of the AVI escapeinterval or expiration of the LRL escape interval, with ventricularpacing inhibited by a sense in the rate ventricle that restarts the LRLescape interval and stops the AVI escape interval. In this mode, thepumping efficiency of the heart will be increased in some patients bysimultaneous pacing of the ventricles with an offset of zero. However,it may be desirable in certain patients to pace one ventricle before theother in order to compensate for different conduction velocities in thetwo ventricles, and this may be accomplished by specifying a particularpositive or negative ventricular offset interval.

FIGS. 2-8 illustrate some of the specific synchronized pacing modes tobe described below. A timeline is shown for each channel, with thechannels designated as RC for rate chamber, SC for synchronized chamber,ARC for atrial rate chamber, ASC for atrial synchronized chamber, VRCfor ventricular rate chamber, and VSC for ventricular synchronizedchamber. In each channel, paces are designated as P, inhibited paces aredesignated as P*, pseudo-paces are designated as P+, and senses aredesignated as S.

FIG. 2 is an example of single-chamber bradycardia pacing withresynchronization, illustrating zero, positive, and negativesynchronized chamber offset intervals (SCO). The VEI is defined as theinterval between the rate chamber paced events while the SCO is definedas an offset of the synchronized chamber (SC) pace from the rate chamber(RC) pace. Negative and positive offset intervals between 0-120 ms maybenefit some patients with severe left or right bundle branch conductiondelays and heart dilatation.

FIG. 3 is an example of dual-chamber bradycardia pacing withresynchronization and various SCOs. The VEI is defined in this case asthe interval between the ventricular rate chamber paced events and theAVI is defined as the interval between the atrial and ventricular ratechamber paced events. The SCO for the atrium is defined as an offset ofthe atrial synchronized chamber and rate chamber paces and the SCO forthe ventricle is defined as an offset of the ventricular synchronizedchamber and rate chamber paces. The atrial and ventricular SCOs can beindependently programmed. FIG. 4 is another illustration of the offsetsynchronized pacing mode in which the second synchronized chamber paceis inhibited by the rate chamber sense. The rate chamber sense resetsthe VEI of the rate chamber and the next scheduled synchronized chamberpace.

In the preferred embodiment, pacing in the paired rate and synchronizedchambers cannot be inhibited or reset during the SCO interval. Thus, ifSCO>0, then after the rate chamber pace occurs, the synchronized chamberpace is committed to occur after the SCO interval. Conversely, if SCO<0,then after the synchronized chamber pace occurs, the rate chamber paceis committed to occur after the SCO interval. Committed SCO pacing canbe implemented by controller logic that ignores any sensing eventsdetected in either paired chamber during the SCO interval (i.e., aconcurrent sensing refractory period), or the SCO interval can beassociated with a concurrent sensing blanking period, during which timesensing in either paired chamber is disabled.

Another resynchronization mode is triggered synchronized pacing. In onetype of triggered synchronized pacing, the synchronized chamber is pacedafter a specified trigger interval following a sense in the ratechamber, as illustrated in FIG. 5A with a trigger interval of zero atthe first RC sense and a non-zero trigger interval at the second RCsense. In another type, the rate chamber is paced after a specifiedtrigger interval following a sense in the synchronized chamber asillustrated in FIG. 5B, with a trigger interval of zero at the first SCsense and a non-zero trigger interval at the second SC sense. The twotypes may also be employed simultaneously. For example, with a triggerinterval of zero, pacing of one chamber is triggered to occur in theshortest time possible after a sense in the other chamber in orderproduce a coordinated contraction. (The shortest possible time for thetriggered pace is limited by a sense-to-pace latency period dictated bythe hardware.) The triggered synchronized pacing mode may be desirablewhen an abnormal intra-chamber conduction time is long enough that thepacemaker is able to reliably insert a pace before depolarization fromone chamber reaches the other. In another case, it may be desirable todelay triggered pacing of the synchronized chamber with a non-zerotrigger interval to mimic the normal physiological conduction delaybetween the two chambers. For example, when the left atrium pacing istriggered by a sensed depolarization in the right atrium, a non-zerotrigger interval can reproduce a physiologically appropriate interatrialconduction delay.

Triggered synchronized pacing can also be combined with offsetsynchronized pacing such that both chambers are paced with the specifiedoffset interval if no intrinsic activity is sensed in the rate chamberand a pace to the rate chamber is not otherwise delivered as a result ofa triggering event. A specific example of the mode is ventriculartriggered synchronized pacing where the rate and synchronized chambersare the right and left ventricles, respectively, and a sense in theright ventricle triggers a pace to the left ventricle and/or a sense inthe left ventricle triggers a pace to the right ventricle.

In a variation of the type of triggered synchronized pacing in which therate chamber is paced after a trigger interval following a sense in thesynchronized chamber, a pace is also triggered immediately to thesynchronized chamber, such as is illustrated in FIG. 7. The advantage ofthis is that the sensed event in the synchronized chamber sensingchannel might actually be a far-field sense from the rate chamber, inwhich case the synchronized chamber should be paced to coordinate withthe rate chamber depolarization. If the synchronized chamber sense wereactually from that chamber, the synchronized chamber pace would occurduring that chamber's physiological refractory period and cause no harm.Similarly, in a triggered synchronized pacing mode in which thesynchronized chamber is paced after a trigger interval following a sensein the rate chamber, a pace may be also triggered immediately to therate chamber as illustrated in FIG. 6. One way of implementing this modeis to control the rate chamber by a triggered bradycardia mode so that asense in the rate chamber sensing channel, in addition to triggering apace to the synchronized chamber, also triggers an immediate ratechamber pace and resets any rate chamber escape interval. In a specificexample, the right and left ventricles are the rate and synchronizedchambers, respectively, and a sense in the right ventricle triggers apace to the left ventricle. If right ventricular triggered pacing isalso employed as a bradycardia mode, both ventricles are paced after aright ventricular sense has been received to allow for the possibilitythat the right ventricular sense was actually a far-field sense of leftventricular depolarization in the right ventricular channel. If theright ventricular sense were actually from the right ventricle, theright ventricular pace would occur during the right ventricle'sphysiological refractory period.

As mentioned above, certain patients may experience some cardiacresynchronization from the pacing of only one ventricle and/or oneatrium with a conventional bradycardia pacing mode. It may be desirable,however, to pace a single atrium or ventricle in accordance with apacing mode based upon senses from the contralateral chamber. This mode,termed synchronized chamber-only pacing, involves pacing only thesynchronized chamber based upon senses from the rate chamber. One way toimplement synchronized chamber-only pacing is to pace the synchronizedchamber and pseudo-pace the rate chamber immediately before expirationof any rate chamber escape intervals, where a pseudo-pace is a zeroenergy or virtual pace used to trigger or terminate timing events withinthe pacemaker. The pseudo-pace thus inhibits a rate chamber pace andresets any rate chamber escape intervals. Such pseudo-pacing can becombined with the offset synchronized pacing mode using a negativeoffset to pace the synchronized chamber and simultaneously pseudo-pacethe rate chamber before expiration of the rate chamber escape interval.The result is that only the synchronized chamber is paced. One advantageof this combination is that sensed events in the rate chamber willinhibit the synchronized chamber-only pacing, which may benefit somepatients by preventing pacing that competes with intrinsic activation(i.e., fusion beats). Another advantage of this combination is that ratechamber pacing can provide backup pacing when in a synchronizedchamber-only pacing mode, such that when the synchronized chamber paceis prevented, for example to avoid pacing during the chamber vulnerableperiod following a prior contraction, the rate chamber will not bepseudo-paced and thus will be paced upon expiration of the rate chamberescape interval. Synchronized chamber-only pacing can be combined alsowith a triggered synchronized pacing mode, in particular with the typein which the synchronized chamber is triggered by a sense in the ratechamber. One advantage of this combination is that sensed events in therate chamber will trigger the synchronized chamber-only pacing, whichmay benefit some patients by synchronizing the paced chambercontractions with premature contralateral intrinsic contractions.

Synchronized chamber-only pacing is illustrated in FIGS. 8A-C for a dualchamber pacing mode. In FIG. 8A, an atrial rate chamber (ARC) sensetriggers an AVI, at the end of which a ventricular rate chamber (VRC)pace would be delivered, but which is inhibited by the ventricularsynchronized chamber (VSC) pace at zero synchronized chamber offset(SCO) and simultaneous VRC pseudo-pace. FIG. 8B is similar, butillustrates timing with SCO<0. In FIG. 8C, an SC sense occurs,initiating a synchronized chamber protection period (SCPP, describedbelow) that inhibits the second scheduled VSC pace, which in turn allowsthe VRC pace to occur in the same cycle. With SCO>0, the rate chamber ispaced first so the synchronized chamber pace does not reset rate chamberpacing. One clinical use of synchronized chamber-only pacing is tosynchronize paced pre-excitation of the synchronized chamber withintrinsic activation of the rate chamber. This will be most effectivewith a dual-chamber pacing mode, where the synchronized chamber is aventricle delayed by bundle branch block and the paired ventricular ratechamber is normally activated by intrinsic atrio-ventricular conduction.Then the AVI and SCO are set as in the examples of FIG. 8A-C to pace theventricular synchronized chamber so that paced and intrinsic activationof the ventricles combine in a beneficial way.

In the resynchronization modes described above, the rate chamber issynchronously paced with a mode based upon detected intrinsic activityin the rate chamber, thus protecting the rate chamber against pacesbeing delivered during the vulnerable period. In order to providesimilar protection to the synchronized chamber, a synchronized chamberprotection period (SCPP) may be provided. The SCPP is a programmedinterval which is initiated by a sense or pace occurring in thesynchronized chamber during which paces to the synchronized chamber areinhibited. For example, if the right ventricle is the rate chamber andthe left ventricle is the synchronized chamber, a left ventricularprotection period LVPP is triggered by a left ventricular sense whichinhibits a left ventricular pace which would otherwise occur before theinterval expires. The SCPP may be adjusted dynamically as a function ofheart rate and may be different depending upon whether it was initiatedby a sense or a pace. The SCPP provides a means to inhibit pacing of thesynchronized chamber when a pace might be delivered during thevulnerable period or when it might compromise pumping efficiency bypacing the chamber too close to an intrinsic beat. In the case of atriggered mode where a synchronized chamber sense triggers a pace to thesynchronized chamber, the pacing mode may be programmed to ignore theSCPP during the triggered pace. Alternatively, the mode may beprogrammed such that the SCPP starts only after a specified delay fromthe triggering event, which allows triggered pacing but prevents pacingduring the vulnerable period.

In the case of synchronized chamber-only pacing, a synchronized chamberpace may be inhibited if a synchronized chamber sense occurs within aprotection period prior to expiration of the rate chamber escapeinterval or synchronized chamber offset interval. Since the synchronizedchamber pace is inhibited by the protection period, the rate chamber isnot pseudo-paced and, if no intrinsic activity is sensed in the ratechamber, it will be paced upon expiration of the rate chamber escapeintervals. The rate chamber pace in this situation may thus be termed asafety pace. For example, in left ventricle-only synchronized pacing, aright ventricular safety pace is delivered if the left ventricular paceis inhibited by the left ventricular protection period and no rightventricular sense has occurred.

An example of synchronized chamber-only pacing is left ventricle-onlysynchronized pacing where the rate and synchronized chambers are theright and left ventricles, respectively. Left ventricle-onlysynchronized pacing may be advantageous where the conduction velocitieswithin the ventricles are such that pacing only the left ventricleresults in a more coordinated contraction by the ventricles than withconventional right ventricular pacing or biventricular pacing. Leftventricle-only synchronized pacing may be implemented in inhibiteddemand modes with or without atrial tracking, similar to biventricularpacing. A left ventricular pace is then delivered upon expiration of theAVI escape interval or expiration of the LRL escape interval, with leftventricular pacing inhibited by a right ventricular sense that restartsthe LRL escape interval and stops the AVI escape interval.

Synchronized pacing may be applied to multiple sites of a singlechamber. In these resynchronization modes, one sensing/pacing channel isdesignated as the rate channel for sensing/pacing a rate site, and theother sensing/pacing channels in either the same or the contralateralchamber are designated as synchronized channels for sensing one or moresynchronized sites. Pacing and sensing in the rate channel follows ratechamber timing rules, while pacing and sensing in the synchronizedchannels follows synchronized chamber timing rules as described above.The same or different synchronized pacing modes may be used in eachsynchronized channel.

Although the invention has been described in conjunction with theforegoing specific embodiment, many alternatives, variations, andmodifications will be apparent to those of ordinary skill in the art.Such alternatives, variations, and modifications are intended to fallwithin the scope of the following appended claims.

What is claimed is:
 1. A method for operating a cardiac rhythmmanagement device, comprising: initiating an atrioventricular escapeinterval based on an atrial event; sensing the right ventricle andgenerating a right ventricular sense upon detection of depolarizationoccurring in the right ventricle; pacing the left and right ventriclesin accordance with expiration of an atrio-ventricular escape interval,wherein the right ventricle is paced upon expiration of theatrio-ventricular escape interval and the left ventricle is paced at apacing instant defined to occur with respect to expiration of theatrio-ventricular escape interval by a specified offset interval; and,stopping the atrio-ventricular escape interval after a right ventricularsense, wherein the atrioventricular escape interval is unaffected bydepolarization occurring in the left ventricle.
 2. The method of claim 1further comprising: sensing an atrium and generating an atrial senseupon detection of a depolarization; and, starting the atrio-ventricularescape interval upon occurrence of an atrial sense.
 3. The method ofclaim 2 further comprising stopping the atrio-ventricular escapeinterval during a cardiac cycle after a right ventricular sense so thatno right or left ventricular pace is delivered during the cardiac cycle.4. The method of claim 2 further comprising: sensing the left ventricleand generating a left ventricular sense upon detection of depolarizationoccurring in the left ventricle; and, inhibiting the left ventricularpace if the pacing instant occurs within a protection period initiatedby a left ventricular sense.
 5. The method of claim 2 furthercomprising: initiating an atrial escape interval based on an atrialevent; pacing an atrium upon expiration of the atrial escape intervalwhich is restarted by an atrial pace or an atrial sense; and, startingthe atrio-ventricular escape interval after an atrial pace.
 6. Themethod of claim 5 further comprising modulating the atrial escapeinterval in a rate-adaptive pacing mode.
 7. A method for operating acardiac rhythm management device, comprising: initiating anatrio-ventricular escape interval based on an atrial event; sensing theright ventricle and generating a right ventricular sense upon detectionof depolarization occurring in the right ventricle; pacing the leftventricle at a pacing instant defined to occur with respect toexpiration of the atrio-ventricular escape interval by a specifiedoffset interval; pseudo-pacing the right ventricle before expiration ofthe atrio-ventricular escape interval to inhibit pacing to the rightventricle; and, stopping the atrio-ventricular escape interval uponoccurrence of a right ventricular sense, wherein the atrio-ventricularescape interval is unaffected by depolarization occurring in the leftventricle.
 8. The method of claim 7 further comprising: sensing anatrium and generating an atrial sense upon detection of adepolarization; and, starting the atrio-ventricular escape interval uponoccurrence of an atrial sense.
 9. The method of claim 7 furthercomprising: sensing the left ventricle and generating a left ventricularsense upon detection of depolarization occurring in the left ventricle;and, inhibiting the left ventricular pace if the pacing instant occurswithin a protection period initiated by a left ventricular sense.
 10. Acardiac rhythm management device, comprising: circuitry for initiatingan atrio-ventricular escape interval based on an atrial event; circuitryfor pacing and sensing the right ventricle and the left ventricle;wherein the left and right ventricles are paced in accordance withexpiration of an atrio-ventricular escape interval, wherein the deviceis configured to pace the right ventricle upon expiration of theatrio-ventricular escape interval and pace the left ventricle at apacing instant defined to occur with respect to expiration of theatrio-ventricular escape interval by a specified offset interval; and,circuitry for stopping the atrio-ventricular escape interval after aright ventricular sense, wherein the atrio-ventricular escape intervalis unaffected by depolarization occurring in the left ventricle.
 11. Thedevice of claim 10 further comprising: circuitry for sensing an atrium;and, circuitry for starting the atrio-ventricular escape interval uponoccurrence of an atrial sense.
 12. The device of claim 10 furthercomprising circuitry for stopping the atrio-ventricular escape intervalduring a cardiac cycle after a right ventricular sense so that no rightor left ventricular pace is delivered during the cardiac cycle.
 13. Thedevice of claim 10 further comprising: circuitry for sensing the leftventricle and generating a left ventricular sense upon detection ofdepolarization occurring in the left ventricle; and, circuitry forinhibiting the left ventricular pace if the pacing instant occurs withina protection period initiated by a left ventricular sense.
 14. Thedevice of claim 11 further comprising: circuitry for initiating anatrial escape interval based on an atrial event; circuitry for pacing anatrium, wherein the atrium is paced upon expiration of the atrial escapeinterval which is restarted by an atrial pace or an atrial sense; and,circuitry for starting the atrio-ventricular escape interval after anatrial pace.
 15. The device of claim 10 further comprising an exertionlevel sensor and circuitry for modulating the atrial escape interval ina rate-adaptive pacing mode.
 16. A cardiac rhythm management device,comprising: circuitry for initiating an atrio-ventricular escapeinterval based on an atrial event; circuitry for sensing the rightventricle and the left ventricle; circuitry for pacing the leftventricle at a pacing instant defined to occur with respect toexpiration of the atrio-ventricular escape interval by a specifiedoffset interval; circuitry for pseudo-pacing the right ventricle beforeexpiration of the atrio-ventricular escape interval to inhibit pacing tothe right ventricle; and, circuitry for stopping the atrio-ventricularescape interval upon occurrence of a right ventricular sense, whereinthe atrio-ventricular escape interval is unaffected by depolarizationoccurring in the left ventricle.
 17. The device of claim 16 furthercomprising: circuitry for sensing an atrium; and, circuitry for startingthe atrio-ventricular escape interval upon occurrence of an atrialsense.
 18. The device of claim 16 further comprising: circuitry forsensing the left ventricle and generating a left ventricular sense upondetection of depolarization occurring in the left ventricle; and,circuitry for inhibiting the left ventricular pace if the pacing instantoccurs within a protection period initiated by a left ventricular sense.